CCR5 and CCR2 polymorphisms and their association with chronic Chagas cardiomyopathy (CCC) in Argentinian population

Abstract

Several studies have proposed different genetic markers as chemokines and cytokines genes for susceptibility to develop CCC. Many genes may be involved, each one making a small contribution. Thus, an appropriate approach for this problematic is to study numerous SNPs in individuals sharing genetic background. Our aim was to analyze CCR2 and CCR5 SNPs located in the promoter region by TaqMan allelic discrimination assay, and their association with CCC in Argentinean populations. A case-control study was carried in 480 T. cruzi seropositive adults from Gran Chaco endemic region and patients attending Buenos Aires hospitals. They were classified in 2 groups according to the Consensus on Chagas-Mazza Disease: non-demonstrated (nonDC) or demonstrated (DC) pathology groups. Due to our studied population did not fit Hardy-Weimberg equilibrium, we subclassified them according to geographical/ethnic origin. Thereby, SNPs frequencies between creole population from endemic regions and Buenos Aires patients were similar but differ from wichi population from Gran Chaco. The association analysis showed that the T allele in rs1800024 was more represented in nonDC than in DC group (p=0.041) in non-wichi population, becoming a protective factor. Among wichi individuals the G allele in rs1800023 was more frequent in DC group (p=0.016) and may be a risk factor to CCC. Moreover, we found that only in wichi population the HHE haplotype displayed a higher prevalence in non-DC group. These results are consistent with a previous study showing that although wichi and creoles live in the same geographical area, they are genetically different and for this reason, the results differed according to the population studied. It is tempting to speculate an association between the above described genetic differences and the clinical manifestations of CCC. Indeed, right bundle-branch block, the most frequent abnormality in CCC, had a clear tendency for lower prevalence in the wichi population.